Despite advances in antibiotic therapy and supportive care, chronic pulmonary infection with Pseudomonas aeruginosa continues to be the major cause of morbidity and mortality in cystic fibrosis. The host response to this infection is characterized by presistent infiltratin of neutrophils (PMNs), but these cells fail to eradicate the infection and may actually cause significant tissue damage. An excessive burden of uninhibitedelastase from PMNs is one of the proposed mechanisms whereby PMNs contribute to lung injury in CF. This project proposes to evaluate an potent protease inhibitor, DMP-777, for potential use in the treatment of CF lung disease. The specific aims are (1) to evaluate the safety and tolerability of multiple doses of DMP-777, (2) to determine the pharmacokinetic and pharmacodynamic characteristics of multiple oral doses, and (3) to define the DMP-777 dosage level necessary to achieve sustained high-level systemic neutrophil elastase inhibition.